Transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells
Transcriptional regulation of BMCC1 mediated by E2F1 in neuroblastoma cells
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DOI：
10.1016/j.bbrc.2016.07.089
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发表时间：
2016-09-09
影响因子：
3.1
通讯作者：
Nakagawara, Akira
中科院分区：
文献类型：
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作者：
Islam, Mohammad Sazzadul;Tatsumi, Yasutoshi;Nakagawara, Akira
在羧基末端区域1（BMCC 1）/PRUNE 2含有BCH基序的分子在有利的神经母细胞瘤（NB）患者中高度表达，编码调节包括RhoA和AKT通路在内的几种信号网络的多功能支架蛋白。越来越多的证据表明BMCC 1是一种肿瘤抑制因子。在这项研究中，我们解决了NBs中BMCC 1转录调控的分子机制。我们发现转录因子E2 F1被募集到BMCC 1基因启动子区的E2 F结合位点。事实上，E2 F1的过表达导致NB细胞系中BMCC 1表达水平的增加。另一方面，在NB细胞中敲低E2 F1产生BMCC 1的下调。此外，我们发现BMCC 1和E2 F1在G1到S相变时同时被诱导。因此，我们得出结论，E2 F1直接促进BMCC 1转录。这些结果表明，E2 F1诱导的BMCC 1通过其促凋亡功能发挥肿瘤抑制作用，导致NB的良好预后。(C)2016 Elsevier Inc. All rights reserved.
BCH motif-containing molecule at the carboxyl terminal region 1 (BMCC1)/PRUNE2 is highly expressed in patients with favorable neuroblastoma (NB), encoding a multifunctional scaffold protein that modulates several signaling networks including RhoA and AKT pathways. Accumulating evidence suggests that BMCC1 acts as a tumor-suppressor. In this study, we addressed molecular mechanism underlying transcriptional regulation of BMCC1 in NBs. We found that transcription factor E2F1 was recruited to E2F-binding site in the promoter region of BMCC1 gene. Indeed, overexpression of E2F1 resulted in an increase in the expression level of BMCC1 in NB cell lines. On the other hand, knockdown of E2F1 in NB cells yielded down-regulation of BMCC1. Also, we showed that BMCC1 and E2F1 were simultaneously induced at G1 to S phase transition. Therefore, we conclude that E2F1 directly facilitated BMCC1 transcription. Taking together, these results suggest that BMCC1 induced by E2F1 acts as a tumor suppressor through its pro-apoptotic function, resulted in favorable prognosis of NB. (C) 2016 Elsevier Inc. All rights reserved.